Bacterial cell culture processes have been developed for the growth of single cell bacteria, yeast and molds which are encased with a tough cell wall. Mammalian cell culture, however, is much more complex because such cells are more delicate and have a more complex nutrient requirement for development. Large scale culture of bacterial type cells is highly developed and such culture techniques are less demanding and are not as difficult to cultivate as mammalian cells. Bacterial cells can be grown in large volumes of liquid medium and can be vigorously agitated without any significant damage. Mammalian cells, on the other hand, cannot withstand excessive turbulent action without damage to the cells and must be provided with a complex nutrient medium to support growth.
In addition, mammalian cells have other special requirements such that most animal cells must attach themselves to some surface to duplicate. On a small scale, mammalian cells have been grown in containers with small microwalls to provide surface anchors for the cells. However, the cell culture for mammalian cells in the containers with microwells generally does not provide sufficient surface area to grow mammalian cells on a large scale basis. To provide greater surface areas, microcarrier beads have been developed for providing surface areas for the cultured cells to attach. Microcarrier beads with attached culture cells require agitation in a bio-reactor vessel to provide suspension of the cells in fresh nutrients. To obtain agitation, such bio-reactor vessels have used internal propellers or movable mechanical agitation devices which are motor driven so that the moving parts within a vessel cause agitation in the fluid medium of the suspension of mammalian cells carried on microcarrier beads.
Bio-reactor vessels with internal moving parts may damage mammalian cells and also subject the cells to high fluid shearing stresses. If the beads collide with one another, the cells can be damaged. One way to reduce the effect of collision o the beads during agitation of the medium in a bio-reactor, is to reduce the density of microcariers in the present bio-reactors which in turn reduces the cell production.
In summary, bio-reactors used to culture mammalian cells typically utilize internal mechanical parts, air, or fluid movement as a lift mechanism to achieve particle suspension. Such mechanism induce damage to growing cells or tissues either directly or indirectly by fluid shear.